scholarly journals MPL Y252H and MPL F126fs mutations in essential thrombocythemia: Case series and review of literature

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmed G. Elsayed ◽  
Aeesha Ranavaya ◽  
Muhammad Omer Jamil
Keyword(s):  
Bone Marrow ◽  
Somatic Mutation ◽  
Essential Thrombocythemia ◽  
Adult Population ◽  
Case Series ◽  
Clinical Importance ◽  
The Other ◽  
Review Of Literature ◽  
Bone Marrow Disease ◽  
Stat Pathway

Essential thrombocythemia (ET) is a clonal bone marrow disease, characterized by increased production of platelets along with other clinical and bone marrow findings. Most patients with ET will have a somatic mutation in one of the known gene locations of JAK2, CALR , or MPL that can upregulate the JAK-STAT pathway. MPL mutation is present in 5% of cases with the most common mutations being W515L and W515K. In this report we describe 2 cases of patients with clinical and laboratory picture of ET. One patient carried MPLY252H mutation which is previously unreported in the adult population but has been shown to be a gain-of-function mutation. The other patient carried MPL F126fs mutation which is not known to be of clinical importance and has not been previously reported.

Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3374-3380 ◽  
Author(s):  
Ruben A. Mesa ◽  
Curtis A. Hanson ◽  
S. Vincent Rajkumar ◽  
Georgene Schroeder ◽  
Ayalew Tefferi
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Quantitative Methods ◽  
Prognostic Significance ◽  
Control Group ◽  
Prognostic Information ◽  
Myeloid Metaplasia ◽  
Bone Marrow Disease ◽  
Myelofibrosis With Myeloid Metaplasia

Abstract Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.

scholarly journals UBA1 and DNMT3A Mutations in VEXAS Syndrome. A Case Report and Literature Review

2021 ◽  
Author(s):  
Farah Shaukat ◽  
Melissa Hart ◽  
Timothy Burns ◽  
Pankaj Bansal
Keyword(s):  
Bone Marrow ◽  
Case Report ◽  
Literature Review ◽  
Gene Mutation ◽  
Clinical Features ◽  
Somatic Mutation ◽  
Review Of Literature ◽  
Unique Case ◽  
Hematological Abnormalities ◽  
Autoinflammatory Condition

Abstract VEXAS syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the UBA1 gene. It often coexists with MDS which can occur due to DNMT3A mutation. These patients, predominantly males, present after the fifth decade of life with unique systemic inflammatory clinical features and have hematological abnormalities and vacuolated precursor cells on bone marrow pathology. Here we describe a unique case of VEXAS syndrome in a patient harboring DNMT3A gene mutation with coexisting UBA1 mutation with a review of literature.

Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3374-3380 ◽  
Author(s):  
Ruben A. Mesa ◽  
Curtis A. Hanson ◽  
S. Vincent Rajkumar ◽  
Georgene Schroeder ◽  
Ayalew Tefferi
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Quantitative Methods ◽  
Prognostic Significance ◽  
Control Group ◽  
Prognostic Information ◽  
Myeloid Metaplasia ◽  
Bone Marrow Disease ◽  
Myelofibrosis With Myeloid Metaplasia

Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.

scholarly journals Essential thrombocythemia in children and adolescents — analysis of 31 cases

2021 ◽  
Vol 66 (4) ◽  
pp. 480-498
Author(s):  
N. M. Ershov ◽  
M. V. Gaskova ◽  
A. V. Pshonkin ◽  
Yu. V. Olshanskaya ◽  
T. V. Konyukhova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Essential Thrombocythemia ◽  
Adult Population ◽  
Disease Onset ◽  
Young Patients ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Asymptomatic Patients ◽  
Number Of Patients

Introduction. Essential thrombocythemia is an extremely rare disorder in childhood. This disease is characterized by a persistent increase in the peripheral blood platelet count, associated with a proliferation of atypical megakaryocytes in the bone marrow.Aim — to analyze the clinical features of the course of essential thrombocythemia (ET) and the response to therapy in pediatric and adolescent patientsMaterials and methods. Thirty-one patients with ET under the age of 21 years were analyzed. All patients were diagnosed with ET in accordance with WHO criteria on the basis of an examination, including assessment of clinical data, laboratory tests (general clinical tests; morphological, genetic, and histological examinations of bone marrow), instrumental studies, and an assessment of response to treatment.Results. The average age of disease onset was 9 years 9 months, with a median of 9 years 6 months. Organomegaly was recorded in 16 (52 %) patients, of whom 6 (37.5 %) had isolated splenomegaly and 6 (37.5 %) had hepatosplenomegaly. Bleeding was noted in 6 (19.4 %) patients with a deep decrease in vWF:RCo (no more than 15 %) and an extreme increase in platelets (PLT) (more than 2000 × 109 /L). Twelve (38.7 %) patients suffered from microcirculation disorders (headaches, dizziness, melalgia), half of them had a platelet count of 1000–2000 × 109 /L, which is comparable to asymptomatic patients. No thrombosis was registered in our group. The JAK2V617F mutation was detected in 3 (9.7 %) patients, a mutation in the CALR gene was found in 9 (29.0 %) of patients, there was a mutation in the MPL gene in one (3.2 %) patient, and in the remaining cases (18 (58.1 %) patients), there was no damage to typical driver genes. Translocation t(12;12) was revealed in 1 (3.2 %) patient. The response to one-component cytoreductive therapy (CR+PR) was found to be quite high in young patients and constituted about 70–80 %. The complete response rate (CR) was as follows, respectively: 42.9 % (3) — to anagrelide therapy (ANA), 47.4 % (9) — to interferon therapy (INF), and 0 % — to hydroxycarbamide (HU). However, HU was not used in the fi rst line of therapy for the children in our group.Conclusion. In the pediatric population, ET patients are dominated by the group of “triple-negative” disease, which somewhat complicates the differential diagnosis with secondary thrombocytosis. Compared to the adult population, the risk of bleeding is higher for pediatric patients, which is associated with the large number of patients with extremely high levels of platelets. In the case of hemorrhagic syndrome development or microcirculatory disorders that cannot be stopped by taking antiplatelet agents, we recommend giving preference to INF and HU as fi rst-line therapy, due to the peculiarities of pharmacokinetics and the potential risk of progression of myelofi brosis during ANA therapy.

Primary bone marrow lymphoma is a rare neoplasm with poor outcome: case series from single tertiary care centre and review of literature

2014 ◽  
Vol 34 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Priyanka Bhagat ◽  
Man Updesh Singh Sachdeva ◽  
Prashant Sharma ◽  
Shano Naseem ◽  
Jasmina Ahluwalia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tertiary Care ◽  
Case Series ◽  
Care Centre ◽  
Review Of Literature ◽  
Tertiary Care Centre ◽  
Rare Neoplasm ◽  
Poor Outcome ◽  
Primary Bone ◽  
Primary Bone Marrow

Venetoclax and Cytarabine in AML Transformed from Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5140-5140
Author(s):  
John McKay ◽  
Matthew Gayhart ◽  
Taha Al-Juhaishi ◽  
Victor Yazbeck ◽  
Edward B. Perkins
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Board Of Directors ◽  
Bone Marrow Biopsy ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Case Series ◽  
The Other ◽  
Advisory Committees ◽  
Acute Myeloid

Background Acute myeloid leukemia (AML) accounts for 1% of all newly diagnosed cancers with a mean age at diagnosis of 68. Although the majority present de novo, AML can be secondary to conditions such as myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). The subset of patients with AML transformed from MPN continues to remain a therapeutic challenge with little data to support clinical efficacy. A large retrospective review of 273 patients revealed no significant improvement in overall survival in this patient population for those diagnosed between 1989 and 2016. Prognosis remains dismal with an overall survival of 5-7 months. Treatment options are limited and often with little proven clinical utility. Even the addition of hypomethylating agents to treatment options has failed to show any improvement in survival necessitating the investigation of new treatment options (Chihara et al, ASH 2016). In this case series, we present two AML cases that have transformed from myelofibrosis and were successfully treated with the combination of cytarabine and venetoclax. Objective Our primary objective was to determine the clinical efficacy of the combination of cytarabine and venetoclax in patients with myelofibrosis with leukemic transformation. Methods This is an observational, retrospective case series of two patients that were treated with cytarabine and venetoclax at Virginia Commonwealth University from 2018 to 2019. Both patients had previously been confirmed as meeting WHO criteria for myelofibrosis on bone marrow examination. Upon transformation to acute myeloid leukemia, again confirmed on bone marrow biopsy, both patients were transitioned to the following regimen: cytarabine 20 mg/m2 on days 1-10 of 28-day cycle in combination with venetoclax with rapid dose escalation to goal of 600mg daily with dose adjustments for medication interactions. The patient's response to therapy and side effect monitoring were performed at regular intervals in the outpatient clinic. Results Our study consisted of two females, age 65 (patient 1) and 71 (patient 2) with a median age of 68 and bone marrow biopsy confirmed diagnosis of myelofibrosis. Both females had grade 3+ fibrosis on marrow examination and both harbored JAK2 mutations on initial diagnosis of myelofibrosis. Patient 2 also demonstrated a 20q deletion. Neither female was deemed a suitable candidate for transplantation due to their age and considerable comorbidities. On transformation to leukemia, blast count burden was 27% and 23%, respectively. Patient 1 had received decitabine prior to the cytarabine/venetoclax regiment while the other had no previous therapy for her myelofibrosis or leukemia. Patient 1 was maintained on the regiment with for 10 months and nearly completed 9 cycles before patient decompensated and was transitioned to comfort care and eventually died. Complications during her treatment course included an elevated uric acid requiring a dose of rasburicase, neutropenic fever and subdural hematoma that resolved without any intervention. Patient 2 has completed 6 cycles of therapy and is now 8 months post initiation of therapy. Her most recent bone marrow biopsy showed a hypocellular bone marrow (20-30% cellularity) and severe myelofibrosis (reticulin 3/3+) with less than 1% blasts. She remains independent of transfusions. Conclusions Our case series demonstrates that the combination of cytarabine and venetoclax can be effectively used in patients with AML transformed from myelofibrosis. In a disease historically with an overall survival of 6 months, one patient survived 10 months and the other is 8 months out and currently in remission from her AML on her most recent bone marrow biopsy, and independent of transfusions. Overall, therapy has been well tolerated with manageable adverse events. Although future prospective studies are needed, the combination of cytarabine and venetoclax offers a reasonable treatment option for secondary AML transformed from myelofibrosis. Disclosures Yazbeck: Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Reversal of DIRECT-ACTING Oral Anticoagulants in Urgent Surgery of the Proximal Aorta: case Series and Review of the literature

2019 ◽  
Vol 24 (38) ◽  
pp. 4534-4539 ◽  
Author(s):  
Eric Zimmermann ◽  
Fawzi Ameer ◽  
Berhane Worku ◽  
Dimitrios Avgerinos
Keyword(s):  
Oral Anticoagulants ◽  
Aortic Surgery ◽  
Management Strategies ◽  
Case Series ◽  
Published Data ◽  
Review Of Literature ◽  
Clotting Factors ◽  
Urgent Surgery ◽  
Direct Acting ◽  
Direct Acting Oral Anticoagulants

Introduction: Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. Literature Search: We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). Case Presentation: We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Conclusion: Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.

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